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Europium-doped NaYF4 nanoparticles cause the necrosis of primary mouse bone marrow stromal cells through lysosome damage

机译:铕掺杂的Nayf4纳米粒子通过溶酶体损伤引起原发性小鼠骨髓基质细胞的坏死

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摘要

Applications of europium-doped NaYF4 (NaYF4: Eu3+) nanoparticles in biomedical fields will inevitably increase their exposure to humans, therefore, the assessment of toxicities must be taken into consideration. It was reported that NaYF4: Eu3+ nanoparticles could accumulate in the bone. However, the potential effect of NaYF4: Eu3+ nanoparticles on bone marrow stromal cells (BMSCs) has not been reported. In this study, NaYF4: Eu3+ particles with diameters of 50 and 200 nm (NY50 and NY200) were prepared and characterized by scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, photoluminescence excitation and emission spectra, and dynamic light scattering. The cytotoxicity of NaYF4: Eu3+ particles on BMSCs and the associated mechanisms were further studied. The results indicated that NaYF4: Eu3+ particles could be uptaken into BMSCs and primarily localized in the lysosome. NaYF4: Eu3+ particles effectively inhibited the viability of BMSCs in a size-dependent manner at 24 and 48 h. After cells were treated with 20 mu g mL(-1) of NY50 and NY200 for 24 h, NaYF4: Eu3+ particles could trigger cell necrosis in a size-dependent manner. The percentage of necrotic BMSCs (PI+/Annexin V-) increased to 15.93 and 14.73%. Necrosis was further verified by increased lactate dehydrogenase leakage. Meanwhile, both NY50 and NY200 induced an increased cell population in the S and G2/M phases. The following mechanism is involved in NaYF4: Eu3+ particle-induced BMSCs necrosis: the NaYF4: Eu3+ particles lead to lysosomal rupture by lysosomal swelling, permeabilization of lysosomal membranes, and increased cathepsins B and D. In addition, NaYF4: Eu3+ particle-induced BMSCs necrosis is also directly caused by the overproduction of ROS through injury to the mitochondria. This study provides novel evidence to elucidate the toxicity mechanisms for bone metabolism and may be beneficial to more rational applications of these nanomaterials in the future.
机译:铕掺杂的Nayf4(NAYF4:EU3 +)纳米颗粒在生物医学领域的应用将不可避免地将其暴露于人类,因此,必须考虑对毒性的评估。据报道,NayF4:Eu3 +纳米颗粒可以积聚在骨中。然而,尚未报道NayF4:Eu3 +纳米粒子对骨髓基质细胞(BMSC)的潜在影响。在本研究中,通过扫描电子显微镜,透射电子显微镜,粉末X射线衍射,光致发光激发和发射光谱,制备直径为50和200nm(NY50和NY200)的NayF4:Eu3 +颗粒,以及动态光散射。进一步研究了NayF4:Eu3 +颗粒的细胞毒性和BMSCs和相关机制的粒子。结果表明,NayF4:Eu3 +颗粒可以被升高到BMSC中并主要在溶酶体中定位。 Nayf4:Eu3 +颗粒在24和48小时的尺寸依赖性方式有效地抑制了BMSCs的活力。在用20μmM10和NY200的NY50和NY200处理细胞后,NayF 4:Eu3 +颗粒可以以尺寸依赖性方式引发细胞坏死。坏死性BMSCs(PI + / Annexin V-)的百分比增加到15.93和14.73%。通过增加乳酸脱氢酶渗漏进一步验证坏死。同时,NY50和NY200都诱导了S和G2 / M阶段的细胞群增加。以下机制涉及Nayf4:Eu3 +粒子诱导的BMSCs坏死:NayF4:Eu3 +颗粒通过溶酶体溶胀,溶酶体膜透露透明化,以及增加的组织蛋白酶B和D.此外,Nayf4:Eu3 +颗粒诱导的BMSCs坏死也直接由对线粒体损伤的RO过量产生引起的。本研究提供了阐明骨代谢的毒性机制的新探讨,并且对未来这些纳米材料的更合理应用可能是有益的。

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  • 来源
    《RSC Advances》 |2016年第26期|共10页
  • 作者单位

    Hebei Univ Coll Chem &

    Environm Sci Key Lab Med Chem &

    Mol Diag Key Lab Chem Biol Hebei Prov Minist Educ Baoding 071002 Peoples R China;

    Hebei Univ Coll Chem &

    Environm Sci Key Lab Med Chem &

    Mol Diag Key Lab Chem Biol Hebei Prov Minist Educ Baoding 071002 Peoples R China;

    Hebei Univ Coll Chem &

    Environm Sci Key Lab Med Chem &

    Mol Diag Key Lab Chem Biol Hebei Prov Minist Educ Baoding 071002 Peoples R China;

    Affiliated Hosp Hebei Univ Baoding 071000 Peoples R China;

    Hebei Univ Coll Chem &

    Environm Sci Key Lab Med Chem &

    Mol Diag Key Lab Chem Biol Hebei Prov Minist Educ Baoding 071002 Peoples R China;

    Hebei Univ Coll Chem &

    Environm Sci Key Lab Med Chem &

    Mol Diag Key Lab Chem Biol Hebei Prov Minist Educ Baoding 071002 Peoples R China;

    Hebei Univ Coll Chem &

    Environm Sci Key Lab Med Chem &

    Mol Diag Key Lab Chem Biol Hebei Prov Minist Educ Baoding 071002 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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